This research proposal is aimed at developing radiopharmaceuticals which concentrate in specific areas of the brain based upon their selective binding to alpha2-adrenergic receptor sites. The goal of this work is to chemically label these agents with the positron emitting radionuclide 18F in order to non-invasively quantitate alpha2-adrenergic receptor sites using positron emission tomography (PET). Of particular interest is imaging the alpha2-adrenergic system of the human cortex, hippocampus, locus coeruleus, and nucleus tractis lateralis. A significant portion of this research will be directed toward the development of novel aromatic nucleophilic fluorination methodology relevant to indane-based radiopharmaceuticals. In addition, 125I-labeled and 123I-labeled alpha2- adrenergic receptor ligands will be developed for in vitro autoradiographic binding studies and as imaging agents for single photon emission computed tomography (SPECT), respectively. It is anticipated that the development of these radiopharmaceuticals will aid in the study of diseases in which aberrations in the alpha2-adrenergic system have been noted such as Alzheimer's disease. These compounds may also be of value in the study of hypertension, drug abuse, depression, diabetes, and other disorders believed to be connected with the alpha2-adrenergic system.